Genomic Organization and Functional Analysis of Murine PKD2L1

Murakami, Manabu; Ohba, Takayoshi; Xu, Feng; Shida, Seiji; Satoh, Eiichi; Ono, Koichi; Miyoshi, Isao; Watanabe, Hiroyuki; Itoh, Hiroshi; Iwamoto, Toshihiko

doi:10.1074/jbc.m411496200

Cited by 50 publications

(41 citation statements)

References 30 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRPP3 may be one of the candidates linked to unmapped human genetic cystic disorders such as dominantly transmitted glomerulocystic kidney disease of postinfancy onset, isolated polycystic liver disease, and Hajdu-Cheney syndrome/ serpentine fibula syndrome (Nomura et al, 1998). Although no evidence showed the direct involvement of TRPP3 in AD-PKD or ARPKD, a role for TRPP3 in cystogenesis is not excluded, as an interaction between TRPP3 and polycystin-1 exists (Murakami et al, 2005). Coexpression of TRPP3 together with polycystin-1 resulted in the expression of TRPP3 channels on the cell surface, whereas TRPP3 expressed alone was retained with the ER (Murakami et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Although no evidence showed the direct involvement of TRPP3 in AD-PKD or ARPKD, a role for TRPP3 in cystogenesis is not excluded, as an interaction between TRPP3 and polycystin-1 exists (Murakami et al, 2005). Coexpression of TRPP3 together with polycystin-1 resulted in the expression of TRPP3 channels on the cell surface, whereas TRPP3 expressed alone was retained with the ER (Murakami et al, 2005). Monolayers formed by ARPKD principal cells of human fetal renal collecting ducts exhibit remarkably higher transepithelial Na ϩ reabsorption than control monolayers (Rohatgi et al, 2003;Olteanu et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…TRPP3 is not a voltage-gated channel, but its channel properties show significant voltage dependence (Chen et al, 1999;Liu et al, 2002). It is noteworthy that coexpression of TRPP3 with polycystin-1, a large receptor-like membrane protein mutated in 80 to 85% of ADPKD, in human embryonic kidney 293 cells resulted in TRPP3 trafficking to the plasma membrane, where TRPP3 seemed to mediate Ca 2ϩ entry in the presence of a hypo-osmotic extracellular solution (Murakami et al, 2005). Coexpression of mouse TRPP3 and polycystin-1L3, an isoform of polycystin-1 with unknown function, but not the expression of TRPP3 or polycystin-1L3 alone, also target to the plasma membrane of human embryonic kidney 293 cells and mediate pH-activated cation conductance (Ishimaru et al, 2006).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of TRPP3 Channel by Amiloride and Analogs

Dai¹,

Ramji²,

Liu³

et al. 2007

Mol Pharmacol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of TRPP3 Channel by Amiloride and Analogs

Dai¹,

Ramji²,

Liu³

et al. 2007

Mol Pharmacol

View full text Add to dashboard Cite

“…49 Therefore, further studies are required to clarify the physiological importance of TRPP3, and to determine the role of TRPP3 in cardiac development. 50 …”

Section: Trpp2 Channels and Cardiac Defectsmentioning

confidence: 99%

The Pathological Role of Transient Receptor Potential Channels in Heart Disease

Watanabe

Murakami

Ohba

et al. 2009

Circ J

Self Cite

View full text Add to dashboard Cite

alcium ion (Ca 2+ ) is a major intracellular messenger with a vital role in many cellular responses. In cardiac myocytes, Ca 2+ not only transmits an electrical signal to the sarcomere thereby triggering a mechanical event, but also induces the expression of genes responsible for hypertrophy or apoptosis. Signaling via Ca 2+ occurs through transient changes in the intracellular Ca 2+ concentration ([Ca 2+ ]i), which is maintained between 10 nmol/L and 10 μmol/L with physiological Ca 2+ transients occurring within this range. The diversity of Ca 2+ -mediated effects is attributable to differences in the amplitude and spatiotemporal pattern of Ca 2+ transients. 1 In cardiac myocytes, intracellular Ca 2+ has 2 origins: the extracellular space and the sarcoplasmic reticulum (SR). The roles of the SR and ryanodine receptors in heart disease have been described by Yano. 2 Here, we focus here on the involvement of Ca 2+ -entry channels in the development of heart disease.The extracellular milieu is a ready source of Ca 2+ , and several ion channels allow Ca 2+ to enter the cell. In cardiac myocytes, voltage-gated Ca 2+ channels (VGCC) mediate Ca 2+ entry upon depolarization of the cell membrane above a threshold potential during an action potential. Ca 2+ entry is mediated partly by the Na + /Ca 2+ exchanger (NCX) running in 'reverse mode'. Other Ca 2+ -entry pathways include ligandgated cation channels (LGC), stretch-activated cation channels (SAC), thermosensitive channels, and receptor-activated cation channels (RAC).LGC are gated by the binding of a ligand to the channel itself. SAC and thermosensitive channels are activated by mechanical stretching and changes in the ambient temperature, respectively. RAC are gated by agonist binding to a receptor distinct from the channel protein. RAC subtypes exist with different Ca 2+ selectivities, activation mechanisms, and physiological functions; these include store-operated Ca 2+ channels (SOC), which are activated upon depletion of the intracellular Ca 2+ store, and receptor-operated Ca 2+ channels (ROC), which are activated by diacylglycerol (DAG).With the exceptions of VGCC and NCX, the molecular identities of Ca 2+ -entry channels have not yet been completely determined, although new findings have emerged in recent years. Novel players regulating Ca 2+ entry have been found in the still-growing family of transient receptor potential (TRP) cation channels. The identification of mammalian TRP channels was a new starting point in the search for the molecular identification of Ca 2+ -entry pathways that contribute to the development of heart disease. This review discusses the expression and function of TRP channels in the heart, their endogenous agonists, the pathophysiological conditions that can modulate these channels, and the potential involvement of TRP channels in the pathogenesis of certain heart diseases such as cardiac hypertrophy, muscular dystrophy associated cardiomyopathy and arrhythmias under Ca 2+ -overload conditions. TRP SuperfamilyDrosophila with mutatio...

show abstract

“…In Xenopus laevis oocytes, TRPP3 targets to the plasma membrane when expressed alone and acts as a Ca 2ϩ -activated channel permeable to Na ϩ , K ϩ , and Ca 2ϩ (15,16). In human embryonic kidney (HEK) cell lines, TRPP3 mainly targets to the endoplasmic reticulum membrane when expressed alone but traffics to the plasma membrane when co-expressed with PKD1 or PKD1L3, a homologue of PKD1 (9,17,18). TRPP3 alone, or together with PKD1L3, mediates pH-dependent cation conductance in an off-response manner, i.e.…”

mentioning

confidence: 99%

Regulation of TRPP3 Channel Function by N-terminal Domain Palmitoylation and Phosphorylation

Zheng¹,

Yang²,

Beauchamp

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Roger ColbranTransient receptor potential polycystin-3 (TRPP3) is a cation channel activated by calcium and proton and is involved in hedgehog signaling, intestinal development, and sour tasting. How TRPP3 channel function is regulated remains poorly understood. By N-terminal truncation mutations, electrophysiology, and Xenopus oocyte expression, we first identified fragment Asp-21-Ser-42 to be functionally important. We then found that deletion mutant ⌬1-36 (TRPP3 missing fragment Met-1-Arg-36) has a similar function as wild-type TRPP3, whereas ⌬1-38 is functionally dead, suggesting the importance of Val-37 or Cys-38. Further studies found that Cys-38, but not Val-37, is functionally critical. Cys-38 is a predicted site of palmitoylation, and indeed TRPP3 channel activity was inhibited by palmitoylation inhibitor 2-bromopalmitate and rescued by palmitoylation substrate palmitic acid. The TRPP3 N terminus (TRPP3NT, Met-1-Leu-95) localized along the plasma membrane of HEK293 cells but stayed in the cytoplasm with 2-bromopalmitate treatment or C38A mutation, indicating that TRPP3NT anchors to the surface membrane through palmitoylation at Cys-38. By acyl-biotin exchange assays, we showed that TRPP3, but not mutant C38A, is indeed palmitoylated. When putative phosphorylation sites near Cys-38 were mutated to Asp or Glu to mimic phosphorylation, only T39D and T39E reduced TRPP3 function. Furthermore, TRPP3NT displayed double bands in which the upper band was abolished by phosphatase treatment or T39A mutation. However, palmitoylation at Cys-38 and phosphorylation at Thr-39 independently regulated TRPP3 channel function, in contrast to previous reports about correlated palmitoylation with a proximate phosphorylation. Palmitoylation at Cys-38 represents a novel mechanism of functional regulation for TRPP3.

show abstract

Genomic Organization and Functional Analysis of Murine PKD2L1

Cited by 50 publications

References 30 publications

Inhibition of TRPP3 Channel by Amiloride and Analogs

Inhibition of TRPP3 Channel by Amiloride and Analogs

The Pathological Role of Transient Receptor Potential Channels in Heart Disease

Regulation of TRPP3 Channel Function by N-terminal Domain Palmitoylation and Phosphorylation

Contact Info

Product

Resources

About